Method for providing disc regeneration using stem cells

ABSTRACT

A method for providing disc regeneration that includes at least partially restoring disc height using a vertebral disc annular fibrosis tensioning and lengthening device, and then injecting a biologic substance, such as stem cells, into the disc that differentiate into chondrocytes and/or notochordal cells that facilitate disc regeneration. Once the biologic substance has regenerated the disc, it may be possible to remove the vertebral disc annular fibrosis tensioning and lengthening device.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part application of U.S. patentapplication Ser. No. 11/646,750, filed Dec. 28, 2006, titled “VertebralDisc Annular Fibrosis Tensioning and Lengthening Device” and claimspriority to U.S. Provisional Patent Application Ser. No. 60/912,869,filed Apr. 19, 2007, titled “Method for Providing Disc RegenerationUsing Stem Cells.”

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to a method for providing discregeneration using a biologic substance and, more particularly, to amethod for providing disc regeneration by injecting stem cells into thedisc after the height of the disc has been at least partially restoredusing a disc annular fibrosis tensioning and lengthening device.

2. Discussion of the Related Art

The human spine includes a series of vertebrae interconnected byconnective tissue referred to as intervertebral discs that act as acushion between the vertebrae. The discs allow for movement of thevertebrae so that the back can bend and rotate.

The intervertebral disc is an active organ in which the normal andpathologic anatomies are well known, but the normal and pathologicphysiologies have not been greatly understood. The intervertebral discpermits rhythmic motions required of all vertebrate animals in theirvarious forms of locomotion. The disc is a high-pressure system composedprimarily of absorbed water, an outer multilayered circumferentialannulus of strong, flexible, but essentially inelastic collagen fibers,and an inner core of a hydrogel called the nucleus pulposus. Theswelling of the contained hydrogel creates the high pressure thattightens the annular fibers and its laminations. Degeneration of discsin humans is typically a slow, complex process involving essentially allof the mechanical and physiologic components with loss of water holdingcapacity of the disc. Discogenic pain arises from either component, butis primarily due to altered chemistry. When this pain is severelydisabling and unyielding, the preferred contemporary treatments areprimarily surgical, particularly fusion and/or disc replacement.

Annular collagen fibers are arranged in circumferential belts orlaminations inserting strongly and tangentially in right- andleft-handed angulated patches into each adjacent vertebral body. Insidethe annular ring is contained an aggrecan, glycosaminoglycan, aprotein-sugar complex gel having great hygroscopic ability to holdwater. The swelling pressure of this gel of the nucleus maintains thepressure within the annulus, forcing the vertebrae apart and tighteningthe annular fibers. This tightening provides the primary mechanicalstability and flexibility of each disc of the spinal column. Further,the angulated arrangement of the fibers also controls the segmentalstability and flexibility of the motion segment. Therefore, the motionof each segment relates directly to the swelling capacity of the gel andsecondarily to the tightness of intact annulus fibers. The same gel isalso found in thin layers separating the annular laminar construction,providing some apparent elasticity and separating the laminations,reducing interlaminar torsional abrasion. With aging or degeneration,nucleus gel declines, while collagen content, including fibrosis,relatively increases.

Disc degeneration, which involves matrix, collagen and aggrecan, usuallybegins with annular tears or alterations in the endplate nutritionalpathways by mechanical or pathophysiologic means. However, the discultimately fails for cellular reasons. It is believed that at an earlyage the central core of the disc, the nucleus pulposus, is made up ofnotochordal cells. These cells lead to the formation of the spinalcolumn and the intervertebral disc. The notochordal cells help to createa proteoglycan matrix that holds water and supports the weight of thevertebral column. As one ages, typically after about 10 years in humans,there is a loss of the notochordal cells within the disc. As these cellsare lost, they are replaced by chondrocytes that make up the maturenucleus pulposus.

There is also a relative decline in the proteoglycan matrix that holdswater. Therefore, the disc begins to dry out or desiccate. As thisprocess progresses, the disc loses its height and water holdingcapacity, and the disc degeneration process begins. The outer fibers ofthe disc starts to get annular tears, leading to further discdegeneration and desiccation. As the disc collapses, the nerves can getprogressively compressed or pinched as they leave the spine, resultingin back pain conditions. Additionally, the back pain can result fromdisc degeneration itself without nerve compression. This condition isnot entirely understood and results in tremendous health dollarexpenditures and loss of worker productivity. Currently, there are notreatment options available to slow down, impede or stop discdegeneration, and it remains a part of the aging process of theintervertebral disc.

Progressive injury and aging of the disc occurs normally in later lifeand abnormally after trauma or metabolic changes. In addition to thechemical effects on the free nerve endings as a source of discogenicpain, other degenerative factors may occur. Free nerve endings in theannular fibers may be stimulated by stretching as the disc degenerates,bulges, and circumferential delamination of annular fibers occurs. Thiscondition may lead to a number of problems. It has been shown that aperson's disc is typically taller in the morning when a person awakes.This phenomenon may be due in part to the reduction of body weightforces on the disc when lying in a recumbent position overnight thatcauses the disc height to restore. Therefore, the reduction ofcompressive forces on the disc may help to restore disc height.

As discussed above, as a person ages, the discs of the spine degenerate,and the disc space height collapses. Further, the ligaments and facetsof the spine degenerate as well. These problems lead to a reduction inthe foramenal height of the vertebrae, often causing central or lateralcanal stenosis. The foramen is an opening through the vertebrae thatallows the nerve from the spinal cord to pass through. Because the nervepasses through the foramen, the nerve will often get pinched as the discheight decreases, leading to various types of back pain. Further, theseproblems often lead to difficulty in walking. Additionally, lateralcanal stenosis causes the nerve to get pinched in the spinal canal.These conditions often lead to neurogenic claudication, where thepatient typically responds by walking shorter distances, then sittingdown, and then flexing the spine by leaning over or by walking with theaid of a device, which helps to flex the spine.

SUMMARY OF THE INVENTION

In accordance with the teachings of the present invention, a method forproviding disc regeneration is disclosed. The method includes at leastpartially restoring disc height using a vertebral disc annular fibrosistensioning and lengthening device, and then injecting a biologicsubstance, such as stem cells, into the disc that differentiate intochondrocytes and/or notochordal cells that facilitate disc regeneration.Once the biologic substance has regenerated the disc, it may be possibleto remove the vertebral disc annular fibrosis tensioning and lengtheningdevice.

Additional features of the present invention will become apparent fromthe following description and appended claims, taken in conjunction withthe accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a pedicle screw employed in a vertebraldisc annular fibrosis tensioning and lengthening device of theinvention;

FIG. 2 is a perspective view of a spring employed in the vertebral discannular fibrosis tensioning and lengthening device of the invention;

FIG. 3 is a side view of the vertebral disc annular fibrosis tensioningand lengthening device of the invention including two of the pediclescrews with the spring therebetween;

FIG. 4 is a cross-sectional side view of the vertebral disc annularfibrosis tensioning and lengthening device shown in FIG. 3;

FIG. 5 is a top view of the vertebral disc annular fibrosis tensioningand lengthening device shown in FIG. 3;

FIG. 6 is a perspective view of a vertebral disc annular fibrosistensioning and lengthening device, according to another embodiment ofthe present invention;

FIG. 7 is a side view showing a vertebral disc annular fibrosistensioning and lengthening device of the invention inserted withinadjacent vertebrae;

FIG. 8 is a top view of two vertebral disc annular fibrosis tensioningand lengthening devices of the invention inserted within the adjacentvertebrae;

FIG. 9 is a side view showing a vertebral disc annular fibrosistensioning and lengthening device inserted within adjacent vertebrae,and a syringe injecting a biologic substance into the disc for discregeneration purposes, according to another embodiment of the presentinvention;

FIG. 10 is a confocal microscope image showing notochordal andchondrocyte differentiated stem cells in a post-injected nucleuspulposus of an animal;

FIG. 11 is a side view of a vertebral disc annular fibrosis tensioningand lengthening device, according to another embodiment of the presentinvention; and

FIG. 12 is a top view of a spring member for the vertebral disc annularfibrosis tensioning and lengthening device shown in FIG. 11.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The following discussion of the embodiments of the invention directed toa method for disc regeneration using a vertebral disc annular fibrosistensioning and lengthening device and a biologic substance is merelyexemplary in nature, and is in no way intended to limit the invention orits applications or uses.

FIG. 1 is a perspective view of a pedicle screw 10 for use in avertebral disc annular fibrosis tensioning and lengthening device (FIG.3) of the invention. The pedicle screw 10 includes a threaded andtapered body portion 12 having a tip 14. The body portion 12 includes aplurality of holes 24 that allow bone to grow therein when the screw 10is threaded into the vertebral body so that the pedicle screw 10 isbetter anchored within the vertebra. The use of holes in the bodyportion of a pedicle screw to facilitate bone growth therein can beemployed in other types of pedicle screws for other uses besidesvertebral disc annular fibrosis tensioning and lengthening devices, suchas spinal fusion pedicle screw and rod instrumentation, well known tothose skilled in the art. The holes 24 can come in a variety of numbers,diameters and configurations. In one non-limiting embodiment, thediameter of the body portion 12 is about 6.5 mm and the diameter of theholes is about 0.5 mm. The pedicle screw 10 can include a bore 26 thatextends through the body portion 12 to make it cannulated so that aK-wire (not shown) can extend therethrough to direct the pedicle screw10 for percutaneous placement over a K-wire previously placed throughthe pedicle into the vertebral body, as is well understood to thoseskilled in the art. The pedicle screw 10 further includes a screw head16 having an extended cup shape defining a cavity 18. The cavity 18includes an open side 20 for reasons that will become apparent from thediscussion below. An annular recess 22 is formed around an outside ofthe head 16 also for reasons that will become apparent from thediscussion below. The pedicle screw 10 can be made of any suitablematerial, such as titanium, as would be well understood to those skilledin the art.

FIG. 2 is a perspective view of a spring 30 having a cylindrical body 32that is also part of the vertebral disc annular fibrosis tensioning andlengthening device of the invention. A series of slots 34 are cut intothe body portion 32, as shown, in an alternating configuration thatallows the body portion 32 to be compressed and provide an expansivespring force. The spring 30 includes generally rounded ends 36 and 38that are shaped to conform to the shape of the inner surface of thecavity 18. The spring 30 can be made of any suitable material for thepurposes described herein, such as nitinol, which is a flexible metalhaving a memory. Other materials may also be suitable, such as a shapememory alloy. An example of a suitable alloy includes about 50% nickeland about 50% titanium.

FIG. 3 is a side view, FIG. 4 is a cross-sectional view, side view andFIG. 5 is a top view of a vertebral disc annular fibrosis tensioning andlengthening device 40, according to an embodiment of the presentinvention. The vertebral disc annular fibrosis tensioning andlengthening device 40 includes two of the pedicle screws 10 where theopen sides 20 of the heads 16 face each other, as shown. The spring 30is inserted into the cavities 18 of the heads 16 so that the ends 36 and38 conform to the inner surface of the cavities 18. The inner surface ofthe cavities 18 and the ends 36 and 38 can be coated with a suitable lowfriction material, such as chrome, cobalt, ceramic, etc., to prevent orreduce wear particle formation as the spring 30 and the pedicle screws10 rub against each other. Initially, the spring 32 is compressed sothat it provides an expansive force to separate the pedicle screws 10.In one non-limiting embodiment, the expanded or relaxed length of thespring 30 is in the range of about 3 cm-4 cm restoring disc height andforaminal height. The diameter of the spring 32 can be any diametersuitable for the purposes described herein.

An oval posterior ring 42 is positioned within the recesses 22, andoperates to maintain the screws 10 in their proper orientation, andprevent the pedicle screws 10 from separating beyond a predeterminedlimit. The fixed diameter of the ring 42 allows for the tips 14 of thepedicle screws 10 to separate greater relative to the heads 16. Thisimparts lordosis. Further, as the spring 30 causes the pedicle screws 10to separate, the ring 42 maintains the top end of the pedicle screws 10stationary to create a pivot and restore the height of the disc andlordosis of the spine. Also, the configuration and orientation of thespring 30, the ring 42 and the screws 10 preserves the motion of thespine as the person performs normal physical movement in that it allowsfor continued flexion, extension, as well as axial rotation of thespine. The spring 30 operates as a compressible link and the posteriorring 42 operates as a rigid link. In one non-limiting embodiment, thering 42 has an axial stiffness from one to 30 million pounds per inch.

FIG. 6 is a perspective view of a vertebral disc annular fibrosistensioning and lengthening device 50, according to another embodiment ofthe present invention, where like elements to the vertebral disc annularfibrosis tensioning and lengthening device 40 are identified by the samereference numeral. In this embodiment, the heads 16 of the pediclescrews 10 include a slot 52. The ring 42 is replaced with a dumbbellmember 54 including a cylindrical body portion 56 and end portions 58and 60. The body portion 56 extends through the slots 52 so that the endportions 58 and 60 are positioned outside of the heads 16, and alsooperates to limit the expansion of the pedicle screws 10 and control theposterior aspects of the screws 10, thus allowing restoration of thelordosis, i.e., normal curvature, of the spine.

FIG. 7 is a side view and FIG. 8 is a top view of two of the vertebraldisc annular fibrosis tensioning and lengthening devices 40 coupled totwo adjacent lumbar vertebra 70 and 72 having a disc 68 therebetween.The pedicle screws 10 are threaded through pedicles 74 of the vertebra70 and 72 and into the vertebral body 76. Once the pedicle screws 10 arein place, then the spring 30 is positioned within the cavities 18 undercompression, as discussed above. As the spring bias forces the vertebra70 and 72 apart, the height of a disc space 78 between the vertebra 70and 72 increases and is restored. Further, as the height of the discspace 78 increases, the disc 68 is able to regenerate due to reducedsheer or compressive forces applied to the disc 68. The device 40creates a controlled distraction force and distraction distance on theannulus fibrosis and a controlled dynamic motion of the vertebra.Further, the device 40 allows motion of the spine while maintaining thestress tension effect on the disc 68. Particularly, the device 40provides a tension force across a compromised vertebral disc providing adistractive force to elicit the stress tension effect on the annulusfibrosis. The pedicle screws and links therebetween are arranged in aparallelogram shape to provide the desired distraction. Because mostsystems work like a hinge, the front or anterior portion of the discmoves much more than the back or posterior portion of the disc torestore lordosis or the natural curvature of the spine. This is not anatural motion, so with the vertebral linkage of the invention, aparallel or near parallel motion of the disc can be achieved. In onenon-limiting embodiment, the motion pathway is an arc of a radius muchlonger than the pedicle screw length. Although the device 40 is showncoupled to adjacent vertebra, the device 40 can extend across anysuitable number of vertebrae to increase the disc space of more than onedisc.

Any suitable surgical procedure for placing the pedicle screws 10 can beused, including minimally invasive percutaneous surgical procedures bymaking the pedicle screws 10 cannulated. In one known process ofpercutaneous pedicle screw instrumentation, a Jamshidi needle is used todock on to the junction of the vertebrae between the facet complex andthe transverse process of the vertebra. Gentle taps with a mallet causethe Jamshidi needle to be advanced through the pedicle 74, making surenot to cross the medial border of the pedicle 74, which can result innerve root injury, until the junction between the pedicle base and thevertebral body is reached. Fluoroscopic visualization into the anteriorposterior and lateral planes of the vertebra is used to see theorientation of the Jamshidi needle. The correct trajectory of theJamshidi needle should place the tip of the needle in the center of thepedicle in the anterior posterior view when the tip of the Jamshidineedle lies at the pedicle vertebral body junction in the lateral view.

Once the junction between the base of the pedicle wall and the vertebralbody is reached, the Jamshidi needle can be directed in a more medialfashion. The Jamshidi needle is typically passed to about one-half thedepth of the vertebral body, and then a K-wire is passed down theJamshidi needle and into the vertebral body a little farther to seat itinto the bone. The Jamshidi needle is then removed. A series ofcannulated muscle dilators are then passed over the K-wire to preventthe soft tissue from going into the threads of the tap. The pedicle istapped and a cannulated pedicle screw is then passed down the dilators.

After the vertebral disc annular fibrosis tensioning and lengtheningdevice 40 has restored some or all of the disc height and has possiblyfacilitated disc regeneration, the present invention also includesfurther facilitating disc regeneration using a biologic substance, suchas stem cells, injected into the disc. Other suitable biologicsubstances may include, but are not limited to, bone morphogenicproteins, condroitin sulfates, synthetic proteoglycan matrixes andcollagens.

FIG. 9 is a side view of the device 40 coupled to the lumbar vertebrae70 and 72 in the same manner as shown in FIG. 7. Also shown is a syringe66 for injecting the biological substance into the disc 68 in apercutaneous manner. Other processes may be applicable for inserting thebiological substance into the disc 68 to biologically restore thedegenerated disc. The device 40 increases the height of the disc 68 asdiscussed above, and provides an area in which the biological substancecan grow within the nucleus of the disc 68. It has been shown that stemcells injected into a disc tend to differentiate along the chondrocytelineage and differentiate into disc material in an in-vivo animal model.This differentiation acts to regenerate the nucleus pulposus in theinner core of the disc 68. It is believed that stem cells willsynthesize the nucleus pulposus of the disc 68 and differentiate intothe chondrocytes and/or notochordal cells in a mature human nucleus. Thedevice 40 may be able to be removed after the disc 68 has beenregenerated by the biological substance.

FIG. 10 is a confocal microscope image showing notochordal andchondrocyte differentiated stem cells in a nucleus pulposus of ananimal. The image was taken some time after the stem cells were injectedinto the disc. The image shows that stem cells have survived anddifferentiated into disc material, including notochordal cells andchondrocytes.

Although the device 40 is used above to restore the disc height andcreate an area for differentiation of the biological substance with thenucleus of the disc 68, the present invention contemplates any suitableexpansive device that separates the vertebrae 70 and 72 to provide thearea for the biological substance to restore the disc 68.

Although a specific type of spring has been described above for thevertebral disc annular fibrosis tensioning and lengthening device, thepresent invention contemplates any linearly expandable link suitable forthe purposes described herein. The link exerts a force creating a stresstension effect within the disc allowing it to regenerate according toWolffs law. The link also allows parallel distraction of the disc,distraction along the coronal plane of the disc tissue, puts the annulusfibrous in tension and provides torsional rotation of the vertebralconstruct. Further, the pedicle screws can be replaced with any suitablemounting member. By a more general description, the vertebral discannular fibrosis tensioning and lengthening device includes a caudalvertebral body attachment member and a cephalad vertebral bodyattachment member having a non-rigid interconnection member therebetweenthat creates the tension stress effect on the annulus fibrosis. Theposterior ring 42 acts as a rigid member coupled between the attachmentmembers that also operates to provide the distractive force andlordosis.

FIG. 11 is a side view of a vertebral disc annular fibrosis tensioningand lengthening device 80, according to another embodiment of thepresent invention. The device 80 includes pedicle screws 82 each havinga screw body 84 and a screw head 86. An annular mounting portion 88 isprovided between the screw head 86 and the screw body 84. The device 80also includes a spring member 90 having a spring 92 and end plates 94and 96. FIG. 12 is a top view of the spring member 90. The spring 92 canbe any suitable spring, such as a helical spring. Holes 98 and 100 areprovided through the end plates 94 and 96, respectively. A U-shapedcoupling member 102 is attached to the end plate 94 and a U-shapedcoupling member 104 is attached to the end plate 96. The U-shapedcoupling members 102 and 104 have a size that conforms to the diameterof the annular mounting portion 88. The surgeon will use a suitable tool(not shown) that is inserted in the holes 98 and 100 to compress thespring 92 and position the U-shaped coupling members 102 and 104 aroundthe annular mounting portions 88 so as to provide a separation force tothe pedicle screws 82 for the reasons discussed above.

As discussed above, the pedicle screws 10 include the holes 24 forfacilitating bone growth therein. Such a concept eliminates or reducesthe halo around the known pedicle screws that reduces the joining of thescrew to the bone. With the holes 24, the screw will act more likenatural bone and increase the integrity of the bonding between the screwand the vertebra, and provide the desired motion preserving affect.

The holes 24 are one example for accepting bone growth in a surgicalscrew. Other configurations can also be employed for pedicle screws, andfor other screws permanently placed in a bony structure to provide boneinterdigitation. Suitable examples include an non-smooth or poroussurface on the screw body, interdigitation cavities formed by theaddition of sintered beads on the outside of the screw body,interdigitation cavities formed by laser processing, interdigitationcavities formed by machining grooves, a roughened surface provided bysand blasting, a hydroxyl appetite coating, etc. Further, the screws arenot limited to pedicle screws, but can be screws for other surgicalapplications, such as maxio-facial applications, hip fractures,podiatric fusions and fraction repair, periarticular fracture fixation,arthroplasty device anchoring, long bone fracture repair, cervicalfusion construct anchoring, tendon anchoring, etc.

The foregoing discussion discloses and describes merely exemplaryembodiments of the present invention. One skilled in the art willreadily recognize from such discussion and from the accompanyingdrawings and claims that various changes, modifications and variationscan be made therein without departing from the spirit and scope of theinvention as defined in the following claims.

1. A method for providing disc regeneration, said method comprising:coupling screws to separate vertebrae; coupling an expansive member tothe screws along a first axis to create a strain on an annular fibrosisof the disc, where the expansive member includes a spring; coupling arigid member to the screws along a second axis offset from the firstaxis, wherein the rigid member is coupled to the screws so that itcreates a pivot force in combination with the expansive member thatcauses tips of the screws to separate more than heads of the screws; andinserting a biological substance into the disc.
 2. The method accordingto claim 1 wherein inserting a biological substance into the discincludes percutaneously injecting a biological substance into the disc.3. The method according to claim 1 wherein inserting a biologicalsubstance in to the disc includes inserting stem cells into the disc. 4.The method according to claim 1 wherein inserting a biological substanceinto the disc includes inserting a biological substance into the discselected from the group consisting of bone morphogenic proteins,condroitin sulfates, synthetic proteoglycan matrixes and collagens. 5.The method according to claim 1 further comprising removing the screwsand the expansive member after the disc has been regenerated by thebiological substance.
 6. The method according to claim 1 wherein thescrews are coupled to the vertebra using minimally invasive surgicaltechniques.
 7. The method according to claim 1 wherein inserting abiological substance into the disc includes inserting the biologicalsubstance into the disc after the disc height has been at least beenpartially restored by the expansive member.
 8. The method according toclaim 1 wherein the screw heads having a cup-shaped cavity and an openarea where the open area of the screw heads face each other, and whereinthe spring includes opposing ends that are positioned within thecup-shaped cavity of the screw heads.
 9. The method according to claim 8wherein the spring includes a cylindrical body between the opposingends.
 10. The method according to claim 9 wherein the cylindrical bodyincludes a plurality of spaced apart slots that allow the spring to becompressed.
 11. A method for providing disc regeneration, said methodcomprising: coupling screws to separate vertebra; coupling an expansivemember to the screws to create a strain on an annular fibrosis of thedisc, wherein the screws include screw heads having a cup-shaped cavityand an open area where the open area of the screw heads face each other,and wherein the expansive member includes a spring having opposing endsthat are positioned within the cup-shaped cavity of the screw heads; andinserting a biological substance into the disc.
 12. The method accordingto claim 11 wherein inserting a biological substance into the discincludes percutaneously injecting a biological substance into the disc.13. The method according to claim 11 wherein inserting a biologicalsubstance in to the disc includes inserting stem cells into the disc.14. The method according to claim 11 wherein inserting a biologicalsubstance into the disc includes inserting a biological substance intothe disc selected from the group consisting of bone morphogenicproteins, condroitin sulfates, synthetic proteoglycan matrixes andcollagens.
 15. The method according to claim 11 further comprisingremoving the screws and the expansive member after the disc has beenregenerated by the biological substance.
 16. The method according toclaim 11 wherein the screws are coupled to the vertebra using minimallyinvasive surgical techniques.
 17. The method according to claim 11wherein inserting a biological substance into the disc includesinserting the biological substance into the disc after the disc heighthas been at least been partially restored by the expansive member. 18.The method according to claim 11 further comprising coupling a rigidmember to the screws.
 19. The method according to claim 18 wherein therigid member is coupled to the screws so that it creates a pivot forcethat causes tips of the screws to separate more than heads of the screwsto provide a lordotic shape to the disc.
 20. The method according toclaim 11 wherein the spring includes a cylindrical body between theopposing ends.
 21. The method according to claim 20 wherein thecylindrical body includes a plurality of spaced apart slots that allowthe spring to be compressed.